Effects of short-term fasting compared to free diet in ovarian cancer patients: Results from a two-arm pilot randomized trial.

5517 Background: Short-term fasting (STF) may enhance chemotherapy efficacy by suppressing insulin-driven pro-survival signaling. Clinical data on the metabolic, oncological, and immunological effects of STF in ovarian cancer (OC) are lacking. Methods: In this prospective, pilot randomized trial conducted at our center, women with advanced high-grade serous OC receiving carboplatin/paclitaxel-based neoadjuvant chemotherapy (NACT) were randomized to STF (36h before to 24h after each cycle) or a free diet (FD). Eligibility criteria included body mass index ≥ 19 kg/m2. Major exclusions were diabetes mellitus, food allergies, and eating disorders. The primary endpoint was insulin reduction after three NACT cycles. Secondary endpoints included oncological outcomes. Exploratory translational analyses assessed immune profiling. Based on 80% power and a two-sided α of 0.05, 17 patients per arm were required. Results: Eighteen patients per arm completed three NACT cycles. Baseline clinical characteristics and insulin levels were comparable between groups. After NACT, insulin increased in FD but decreased in STF (+9.76 vs -1.12 µIU/mL; p=0.01). Patients who did not undergo interval cytoreductive surgery (ICS) after three cycles experienced a greater insulin increase than those who underwent surgery (+11.46 vs +1.35 µIU/mL; p=0.033). At ICS, a chemotherapy response score of 3 was more frequent in STF than in FD (58.8% vs 17.6%; p=0.03). After a median follow-up of 18 months, median progression free survival (PFS) was longer in the STF arm compared with FD (38 vs 24 months; p=0.045). Translational analyses showed that STF limited immunosuppressive subsets correlated with chemotherapy response. Conclusions: The primary endpoint was met. STF induced a favourable metabolic shift and was associated with improved pathological response and prolonged PFS, alongside immune modulation. These findings provide a strong rationale for larger randomized trials evaluating STF in OC. Clinical trial information: NCT07039331 . Surgical outcomes and metabolic parameters before (baseline insulin levels) and after neoadjuvant chemotherapy (insulin levels and variation after NACT) according to the diet regimen. Free Diet Arm N=18 Short-Term Fasting Arm N=18 Overall population N=36 P value ICS Never 1 (5.6) 1 (5.6) 2 (5.6) 0.927 After III cycles 12 (66.7) 13 (72.2) 24 (66.6) After VI cycles 5 (27.7) 4 (22.2) 8 (22.2) CRS 1 5 (29.4) 1 (5.9) 6 (17.6) 0.030 2 9 (52.9) 6 (35.3) 15 (44.1) 3 3 (17.6) 10 (58.8) 13 (38.2) Insulin Level - Baseline (µIU/mL) Mean, SD 8.7 (4.99) 10.7 (7.54) 9.71 (6.38) 0.353 Insulin Level - after NACT ( µIU/mL) Mean, SD 18.5 (12.68) 9.59 (6.66) 14.03 (10.95) 0.014 <jats:td colspan="2" content-type="r